Thymus-derived lymphocytes (T cells) play an important role in the immune response to most antigens. The function, for the most part, by modulating the immune response. The molecular basis for this immunoregulation is currently unknown. High or low response to various thymic-dependent antigens is determined by genes located in the I region of the major histocompatibility (H-2) complex of the mouse. I-region associated molecules (Ia antigens) are expressed on the surfaces of cells intimately involved in the regulation and generation of both cellular and humoral immunity. A new locus, Ia-4, has recently been described for a segment of the I region known as the I-J subregion. The I-J subregion encodes for determinants predominantly found on suppressor T cells and their soluble products (i.e. suppressor factors). We have recently produced monoclonal antibodies directed against I-J gene products. These monoclonal anti-I-J antibodies affect (inactivate?) suppressor T cells both in vivo and in vitro by allowing nonresponder mice to respond to injection of poly(glu50tyr50)(GT). Further, some, but not all, of these haplotype specific monoclonal anti-I-J antibodies bind a soluble GT-specific T cell-derived suppressor factor (GT-TsF). This suggests that our monoclonal anti -I-J antibodies may be directed against different gene products of the I-J subregion, gene products which are expressed on different subpopulations of T cells or their factors. We plan to characterize the heterogeneity of I-J gene products both functionally and biochemically using our monoclonal anti-I-J antibodies. Effect of monoclonal anti-I-J antibodies on T cell and macrophage functions will be assessed in vitro using a modified Mishell-Dutton type culture system. Antibody responses will be measured on the cellular level using a hemolytic plaque assay. We plan to determine the role of the I-J gene products in the regulation of the humoral immune response to the synthetic polyamino acid GT. In addition, we have produced a monoclonal GT-TsF. This GT-TsF is a gene product of the I-J subregion and is recognized by our monoclonal anti-I-J antibodies. Monoclonal anti-I-J antiboides and monoclonal GT-TsF provide us with powerful tools for the biochemical characterization of a functional I-J product.